Original research••

Tranexamic acid and tourniquet versus tourniquet for controlling blood loss during open abdominal myomectomy: a double-blind placebo-controlled randomised trial

•,,,,,,,.

...

Abstract

Objectives To compare blood loss in reproductive-age women who received intravenous tranexamic acid plus tourniquet versus tourniquet and placebo during an open abdominal myomectomy.

Methods This is a prospective three-centre double-blind randomised placebo-controlled trial of consenting eligible 114 women with uterine fibroids scheduled for open abdominal myomectomy. The participants were randomised equally (ratio of 1:1) to receive either 1 g of intravenous tranexamic acid plus tourniquet (study group) or tourniquet plus placebo (control group) during the procedure. The primary outcome measure was the volume of intraoperative blood loss in both groups, while the secondary outcome measures were the mean volume of total blood loss, the mean difference between preoperative and postoperative haemoglobin, and the rate of intraoperative and postoperative blood transfusion in both groups.

Results The demographic characteristics of the participants enrolled in this trial were homogenous at baseline, and there was no significant difference in the mean intraoperative blood loss between the study and control groups (578.53±142.59 mL vs 629.35±174.13 mL; p=0.09). The mean total blood loss (1016.30±233.4 mL vs 1128.47±282.85; p=0.02), the rate of intraoperative (5.3% vs 33.3%, p<0.01) and postoperative (1.8% vs 22.8%, p=0.01) blood transfusions, respectively, were significantly lower in the study group than the control group. However, the mean difference in haemoglobin concentration was significantly higher in the study group than in the control group (1.97±0.47 g/dL vs 2.49±0.73 g/dL; p<0.01).

Conclusion Intraoperative tranexamic acid as an adjunct to a tourniquet is associated with a significant reduction in both the mean total blood loss and the necessity for blood transfusions during open abdominal myomectomy procedures.

Trial registration number PACTR202312679640849.

What is already known on this topic

Open abdominal myomectomy is a common surgical option for treating symptomatic uterine fibroids, though it often leads to significant blood loss. To prevent complications, both pharmacological and mechanical techniques are employed to reduce blood loss during surgery. Despite this, the use of tranexamic acid as an adjunct to the tourniquet is not commonly practised during open abdominal myomectomy.

What this study adds

This study demonstrates that tranexamic acid, a potent antifibrinolytic agent, when used alongside the traditional tourniquet, significantly reduces total blood loss and decreases the need for blood transfusions during open abdominal myomectomy compared with using the tourniquet alone.

How this study might affect research, practice or policy

In the absence of contraindications, incorporating tranexamic acid as a routine adjunct to the conventional tourniquet should be promoted, particularly in settings where open abdominal myomectomy for large uterine fibroids is prevalent, and anaemia remains a significant contributor to maternal morbidity and mortality.

Introduction

Uterine fibroids are the most common non-cancerous gynaecological tumour in women of childbearing age.1 It is estimated that 20–30% of women aged 30–50 have uterine fibroids.2 Uterine fibroids are also responsible for 9.8% of new gynaecological admissions in a tertiary hospital in Nigeria,3 and 52.29% of hysterectomy specimens were diagnosed with uterine fibroids.4

Abdominal myomectomy remains one of the treatment modalities for symptomatic uterine fibroids.5 Laparotomic myomectomy is one of the surgical options for patients wishing for pregnancy.6 In low and middle-income countries, open abdominal myomectomies are common, mainly because of the size and multiplicity of the fibroids in the patients at presentation.7 8 Different incidence rates of abdominal myomectomy have been documented in different parts of the world, and it exhibits considerable geographical variability influenced by genetic, environmental and healthcare-related factors.9–11

Myomectomy, just like every other procedure, is associated with complications. Intraoperative complications include haemorrhage, the need for blood transfusion and its attendant complications, injury to other organs, conversion to hysterectomy and anaesthetic complications.8 12 Haemorrhage has been variously reported as a major cause of morbidity and mortality among women who had an open abdominal myomectomy,13 and blood transfusion can be required in up to 20% of women during abdominal myomectomy.14 Morbidity associated with haemorrhage during myomectomy includes postoperative anaemia, fever, conversion to hysterectomy and complications arising from blood transfusion.7

While abdominal myomectomy is associated with low mortality rates globally, these rates vary based on healthcare infrastructure, surgical expertise and patient health conditions. Continued improvements in surgical techniques, perioperative care and healthcare access are essential to further minimise the risk of mortality associated with this procedure.15

It is important to take various measures to minimise blood loss during and after open myomectomies. The general approach involves making dissections along avascular planes whenever possible. The avascular planes are nothing other than the myoma pseudocapsule. Therefore, the myomectomy should be done inside the pseudocapsule (intracapsular myomectomy), to avoid excessive blood loss. Both mechanical and pharmacological methods are employed to reduce blood loss during myomectomy. The use of a tourniquet has been proven to significantly decrease blood loss during open abdominal myomectomy.16 In low and middle-income countries, tourniquets are often created using an improvised Foley catheter, which is both safe and cost-effective.17

On the other hand, various pharmacological agents have been employed to reduce blood loss during an open abdominal myomectomy. Some pharmacological agents used to reduce blood loss during open abdominal myomectomy include vasopressin, epinephrine, uterotonics (like misoprostol) and tranexamic acid.7 18 These pharmacological agents have different mechanisms for achieving reductions in blood loss during and after surgery. Tranexamic acid, an antifibrinolytic agent, is a promising drug for the reduction of blood loss during myomectomy.

Tranexamic acid is a synthetic derivative of the amino acid lysine that exerts its antifibrinolytic effect through the reversible blockade of the lysine binding sites on plasminogen. It can be administered through various routes, which include the oral route, the parenteral route and the topical route. It is useful in a wide range of haemorrhagic conditions, such as cardiopulmonary bypass surgery and haemorrhage associated with dental extraction.19 20 The adverse effect is rare and has not been reported in a clinical trial.18 Some studies have shown that the administration of tranexamic acid is associated with reduced perioperative blood loss. For instance, tranexamic acid has been shown to reduce blood loss and also decrease the rate of blood transfusion during surgical procedures in cardiac surgeries, orthopaedic surgeries, organ transplantations21 22 and oral maxillofacial surgeries.19 Its use in obstetrics for the control of postpartum haemorrhage has also been reported,23 while in the field of gynaecology, it is used in treating menorrhagia.9 Considered a safe adjunct for myomectomy and other gynaecological procedures, tranexamic acid in several recent randomised control studies, systematic and meta-analyses has been demonstrated to shorten operating times, minimise blood loss and related complications, lower the need for blood transfusions and shorten hospital stays.24–28

Furthermore, the use of tranexamic acid during open abdominal myomectomy to minimise blood loss is widely adopted in many health institutions, but the evidence is unclear. Though the information on the use of tranexamic acid alone without a tourniquet is scanty, it has been reported in a study on the use of both intravenous and topical tranexamic acid, which has shown a reduction in mean blood loss and a reduction in the need for blood transfusion during open myomectomy.18 It is noteworthy that most of the studies on efforts to reduce blood loss during myomectomy used tourniquets or intravenous tranexamic acid independently.29 Studies on the use of tranexamic acid plus tourniquets are scanty. Also, some of the previous studies had limitations such as a small sample size and difficulty with the estimation of blood loss.17

The use of a tourniquet alone during an open myomectomy does not remove the challenge of intraoperative blood loss in Nigeria.30 Considering the morbidity that affects the quality of life and mortality arising from myomectomy-associated blood loss, there is a need to look out for interventions that could further reduce blood loss during the procedure. Therefore, combining a tourniquet with intravenous tranexamic acid is anticipated to further significantly reduce blood loss, particularly in low and middle-income countries where large and multiple uterine fibroids are prevalent.31 This study will compare the effectiveness of using both a tourniquet and tranexamic acid versus a tourniquet alone in reducing blood loss during open myomectomies in tertiary hospitals in Nigeria.

Methods

Study design

This is a prospective three-centre, double-blind randomised placebo-controlled trial.

Study settings

The study was carried out at the Department of Obstetrics and Gynaecology, University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu, Enugu State University Teaching (ESUT) Hospital Parklane, Enugu and Mother of Christ Specialist Hospital (MOCSH) Enugu, Nigeria, between 2 January 2024 and 2 May 2024.

Study participants

The participants were drawn from women in the reproductive age group attending the gynaecology clinics of both UNTH, ESUTH and MOCSH who had uterine fibroids and were booked for myomectomy in the study centres.

Inclusion criteria

Women of reproductive age with symptomatic uterine fibroids booked for open abdominal myomectomy at the study centres were recruited for this study.

Exclusion criteria

Those excluded from the study were patients with a history of myomectomy in the past, use of the gonadotropin-releasing hormone (GnRH) analogue before surgery, allergy to the use of tranexamic acid, thromboembolic disorders, renal impairment and those who are obese (weight>30 kg/m²).

Sampling method

A multistage sampling technique was used in this study. All three recruitment centres were specifically chosen for the study at the initial sampling stage. In the subsequent sampling phase, the number of participants for each research centre was assigned using the proportionate sampling technique, which took into account the total number of myomectomies performed by each centre in the preceding two consecutive years. Using a ratio of 9:9:6, representing the number of myomectomies per month at UNTH, ESUTH and MOCSH, respectively, 37.5% of the sample size was allocated to UNTH and ESUTH study centres, while 25% was allocated to MOCSH.

In the third stage of the sampling, convenient sampling techniques were used to recruit participants in each study centre until the required sample size was achieved. All eligible and consenting women of reproductive age booked for open myomectomy at the study centres were recruited into the study. All the participants passed through history-taking and general, abdominal and vaginal examinations. Body mass index (BMI) was calculated, and abdominopelvic ultrasound was done to confirm and rule out other possible causes of abdominal swelling. It also provided information on the size of the fibroid nodules, the number of fibroid nodules, their type and their locations.32

Sample size calculation

The following steps were used in the calculation of the minimum sample size of the study participants. The total number of participants in the study, n=2 n,33 n was calculated as follows:

$Display Formula$

d=moderate effect size. Employing an attrition rate of 10%, the calculated minimum sample size for both groups was 114 (57 in each group).

Randomisation and blinding of the participants

An independent statistician generated two sets (A and B) of random numbers from 1 to 114. Opaque envelopes were numbered sequentially from 1 to 114. The random set (A or B) corresponding to each number was written on the same size of paper and enclosed in the corresponding envelope. These envelopes were kept by a senior registrar not involved with the study. Once an eligible woman consented to the study, a serial number was assigned to her. The research assistant keeping the envelope opens the envelope corresponding to the participant’s serial number and announces the letter (A or B) in the envelope for the study. The participants were allocated into groups corresponding to letters, thus, Group A (tranexamic acid group plus tourniquet) and Group B (tourniquet group and placebo).

The participants and the investigator were not aware of the group the participants belonged to, hence double-blinded. All the participants received pericervical tourniquets. A trained research assistant (a pharmacist) drew the appropriate volume of each drug (tranexamic acid or sterile water) into a 10 mL syringe labelled with the patient’s name. Those in Group A received intravenous tranexamic acid of 1 g over 10 min, 20 min before surgery, administered by a resident in the ward, while those in Group B received sterile water (placebo) of appropriate volume. The intraoperative blood loss was estimated by the research assistant (trainee resident doctor in obstetrics and gynaecology), who was blinded to the study objective. Four research assistants were trained over a period of 4 weeks in each centre for the study. All randomised participants, regardless of adherence or drop-out, were included in the final analysis.

Measurement of surgical materials

All mops (each measuring about 50×50 cm), gauze (measuring 10×10 cm) and drapes were weighed in grams using a high-precision weighing scale (Camry digital kitchen weighing scale), which will be standardised before use to ensure it remains accurate.34 The weighing was done in such a way that strict adherence to aseptic procedures was maintained. The mops were measured individually. Weight per unit was noted; the same applies to the gauze that was used (1 g=1 mL).7 The drapes, which comprised four small surgical towels and one large drape, were weighed together and the total weight was taken. After the procedure, drapes were remeasured, the difference was noted and the conversion was done via the gravimetric method.7

Study procedure

Eligible participants allocated to group A (the tranexamic acid group together with the tourniquet) received 1 g of intravenous tranexamic acid by slow intravenous infusion over 10 min, 20 min before the skin incision and another 25 mg/kg/day in three divided doses each in 1 L of normal saline for 24 hours after the surgery at a rate of 40 drops per min (Trexam, (PROTECH) brand of tranexamic acid was used in this study). The control group received a tourniquet with a placebo (sterile water).

The technique for open abdominal myomectomy that was used in this study is the one described by Bonney and modified by Hudson.7 This technique was adopted in our practice at UNTH and in the other two study centres. Surgery was done by consultants and senior registrars in the three centres. All participants received prophylactic antibiotics, intravenous ceftriaxone (1 g statim) and infusion metronidazole (500 mg) 30 min before the procedure. The patients were placed in a supine position, and the abdomen was cleaned twice with a chlorhexidine solution, dried once and methylated spirit applied before drapes were placed. The abdominal incision was a Pfannenstiel or subumbilical midline incision with extension above the umbilicus as appropriate; however, the incision to make was dependent on the size of the uterus. As soon as access was gained into the peritoneal cavity, a general inspection was done, the uterus was lifted out of the pelvic cavity and a thorough inspection of the uterus, fallopian tubes and ovaries was carried out. A 24-gauge Foley catheter that was provided for each participant was applied to the base of the uterus, close to the insertion of the uterosacral ligament. This was made tight by the application of strong Kochers forceps anteriorly. This temporarily impeded the blood supply from the uterine and ovarian arteries. And this was released every 30 min to prevent irreversible ischaemic injury to the uterus.17

Enucleation of the fibroid nodule was done via an anterior uterine incision as much as possible. After enucleation, the dead spaces were properly closed using Vicryl 2 sutures. A fenestrated, closed drain was inserted at the Pouch of Douglas. This was achieved by creating a fenestration of about 1 cm in diameter and 1 cm apart on the size 24 Foley catheter with a urine bag attached to its end. This accounted for the collection of bloody effluent that occurred immediately after the abdomen was closed. The anterior abdominal wall was repaired in layers using continuous Vicryl 2–0 for the peritoneum and the subcutaneous layer, continuous Vicryl 2 or Nylon 2 for the rectus sheath and subcuticular Vicryl 2–0 for the skin. The operation site incision was dressed in gauze and firm plaster was applied.

The measurement of blood loss was done by the researcher or trained research assistant, who was blinded to the group to which the patients belonged. The blood in the abdominal drain was emptied into a standard calibrated measuring cylinder, and the accurate volume in millilitres was measured. Used gauze, mops and drapes were reweighed immediately; they were dropped using a standard weighing scale. The gravimetric method was used for conversion (1 g=1 mL).7 So the difference in weight in grams was converted to millilitres, and the total blood loss intraoperatively was the difference in weight (gram) of mops, gauze and drape converted to millilitres plus the volume of blood in the suction-calibrated bottle.

A designed pro forma was used by the investigator, who was blinded to the group the participant belongs to, for data collection. The participant was expected to respond verbally to a question on sociodemographic variables. The intraoperative blood loss was recorded by a senior registrar in anaesthesia who participated in the surgery and was blinded to the group to which the patient belongs. The difference in weight of the mop, gauze, drapes and surgical towels used during the surgery in grams was converted to volume in millilitres and added to the volume of blood in the suction bottle. Postoperative blood loss was derived from the volume of blood in the drain. Preoperative haemoglobin was recorded the morning before surgery, while postoperative haemoglobin was done 2 days postoperatively. Both were done in a standard laboratory (UNTH main lab, ESUTH main lab and MOCSH lab) for an accurate result. The number of pints of blood given intraoperatively and postoperatively was documented before discharge. Any side effects concerning the tranexamic acid used were documented.

Outcome measures

The primary outcome measure was the volume of intraoperative blood loss in millilitres in both groups, while the secondary outcome measures were the mean volume of total blood loss in millilitres in both groups, the mean difference between preoperative and postoperative haemoglobin in g/dL in both groups and the rate of blood transfusion in both groups.

Statistical analysis

The analysis was both descriptive and inferential at a 95% confidence level using IBM Statistical Package for Social Sciences V.22.0 computer software. Continuous variables were presented as mean±SD and compared using the Student’s t-test. Categorical variables, where applicable, were analysed using Pearson’s χ². A p value of 0.05 was considered to be statistically significant. Analysis was by intention-to-treat.

Results

Out of 116 eligible participants who were counselled for the study, 114 consented and were randomised into two groups: the study group (tranexamic acid plus tourniquet) and the control group (tourniquet plus placebo). Two participants opted out of the study on account of an allergy to tranexamic acid. All the participants who started the study completed it. This is shown in figure 1.

Figure 1

Request permission

Study flow diagram.

The mean age of the participants was 33.70±5.09 and 34.7±5.22 years for the study and control groups, respectively. There was no significant difference between the two groups with respect to the educational status, religion, tribe or employment status of the participants. The other details in the sociodemographic variables of the participants in the two groups are as shown in table 1.

Table 1

•

Sociodemographic characteristics of respondents

Table 2 shows that the reproductive and other basic characteristics of participants were similar between the study and control groups. The majority of the participants in each group were nulliparous (54.4% vs 57.9%) and overweight (86.0% vs 78.9%) with mean BMI (26.40±1.49 vs 26.22±1.45 kg/m²). The median uterine size at presentation for the two groups was similar (23 vs 24 weeks), with an IQR (20–28 vs 18–28 weeks). The most common indications for myomectomy in the two groups were abdominal swelling (86.0% vs 87.7%) and menorrhagia (84.2% vs 84.2%).

Table 2

•

Reproductive characteristics of the respondents

As shown in table 3, the study group (tranexamic plus tourniquet) showed a reduction in mean intraoperative blood loss (578.53±142.59 mL) compared with the control group (tourniquet plus placebo) (629.35±174.13 mL); however, the difference was not statistically significant (p=0.09). The study group showed a statistically significant reduction in postoperative blood loss based on blood in the wound drain compared with the tourniquet plus placebo group (441.23 mL vs 495.61 mL; p=0.01). There was a significant difference in the mean total blood loss (intraoperative and postoperative) between the tranexamic acid plus tourniquet group when compared with the control group (1016.30 mL vs 1128.47 mL; p=0.02). The mean postoperative haemoglobin concentration was significantly higher in the study group compared with the control group (9.09 g/dL vs 8.77 g/dL; p=0.01). There was also a significant difference in the mean haemoglobin concentration between the tranexamic acid plus tourniquet group and the tourniquet plus placebo group (1.97 g/dL vs 2.49 g/dL; p<0.01). The control group had a higher mean difference in haemoglobin concentration compared with that of the study group. This is shown in table 3.

Table 3

•

Comparison of the mean perioperative blood loss and haemoglobin levels between participants in the tranexamic acid and tourniquet group and control group

The rate of intraoperative (5.3% vs 33.3%; p<0.01) and postoperative (1.8% vs 22.8%; p=0.01) blood transfusions respectively were significantly lower in the tranexamic acid plus tourniquet group compared with the control group. This is shown in table 4.

Table 4

•

Comparison of the blood transfusion rate of women who received tranexamic acid and tourniquet versus tourniquet alone intra and post myomectomy

Discussion

The major finding of the study was that the intraoperative blood loss during open myomectomy was similar between the study and control groups; however, the total blood loss was significantly lower in the tranexamic group when compared with the control. This observed difference in the total blood loss reflected on the participants’ haemoglobin difference (postoperative minus preoperative) and blood transfusion rates, which also significantly differed between the two groups.

There was no significant difference in the mean intraoperative blood loss between the study group (intravenous tranexamic acid plus tourniquet) and the control group (tourniquet plus placebo). This could be attributed to the onset and duration of action of intravenous tranexamic acid. Evidence has shown that the onset of action of intravenous tranexamic acid starts from a few minutes after injection to a peak maximal effect of about 3 hours.35 The mean duration of surgery in the study group (98.7 min) fell below the time of maximal effectiveness of the drug; therefore, the maximal haemostatic potential may not have been fully effective in reducing blood loss intraoperatively. The finding in this study was similar to that of Caglar et al in a randomised control study in Turkey involving 100 consenting women of reproductive age undergoing abdominal myomectomy, where they found that the mean intraoperative blood loss was 654 mL versus 820 mL in the study and control groups, respectively; however, there was no significant difference between the two groups.36 Similarly, Abdul et al in the adjunctive use of tranexamic acid to tourniquet in reducing haemorrhage during abdominal myomectomy in Ilorin, Kwara State, Nigeria, found no significant difference between the groups studied (tourniquet plus intravenous tranexamic acid and tourniquet plus placebo) (907.25 mL±529.8 vs 998.72 mL±607.21, p=0.475), respectively, in terms of the mean intraoperative blood loss.37 The observed insignificant reduction in intraoperative blood loss in these (and related) studies may still suggest that there could be further reduction in the morbidity of women who are undergoing myomectomy. This effect may be more pronounced with a larger population and therefore calls for larger studies and meta-analyses in our environment. The finding of the present study was also similar to that of Ngichabe et al in a study to determine the effect of intravenous tranexamic acid as an adjunct haemostasis to ornipressin during open abdominal myomectomy in Nairobi, Kenya. The finding, in terms of mean intraoperative blood loss, was found to be (251 mL vs 398 mL; p=0.361) between the study and control group,38 and this was not statistically significant. The two groups received a vasoactive agent in the form of ornipressin as haemostat. It is noteworthy that ornipressin was used in place of tourniquet in this particular study, thereby suggesting the possibility of tranexamic acid playing an important role in further reducing blood loss during myomectomy in women.

Nevertheless, similar studies by Shaaban et al in Ismaili, Egypt, and Nahla et al in Aswan, Egypt, found a statistically significant difference in the mean intraoperative blood loss between the intravenous tranexamic (study) and placebo (control) groups.18 39 It is possible that the different methodologies used in the above studies contributed to the reported differences. For instance, three groups were compared in the Nahla et al study, and topical tranexamic acid was used during that study. However, their study still showed that tranexamic acid could be potentially useful in controlling blood loss during myomectomy. It may also show that, irrespective of the route of administration, tranexamic acid could be useful in myomectomy for controlling blood loss.

As revealed in the present study, the study group (tourniquet plus intravenous tranexamic acid) experienced significantly lower mean total blood loss (both intraoperative and postoperative) compared with the control group. This supports the explanation regarding the peak onset of intravenous tranexamic acid’s action and its extended antifibrinolytic effect.35 The mean terminal half-life of tranexamic acid is between 8 and 11 hours postadministration, aligning with the time of patients’ transition from surgery to the ward. The antihaemorrhagic effect of intravenous tranexamic acid was particularly effective in reducing postoperative and thus total blood loss when administered according to the study’s regimen. This significant reduction in total blood loss mirrors findings from similar studies conducted in Egypt18 39 and Turkey.36 It therefore shows that tranexamic acid with good surgical skills will help further reduce blood loss during myomectomies among women. This is very important in developing countries where blood transfusion services could be limited by both their availability and costs.

Contrary to this study’s findings is the report from Washington, USA,14 which found no statistically significant difference in terms of total blood loss between the tranexamic acid and placebo groups (p=0.88). Notably, the authors used different approaches for myomectomy (ie, laparoscopic, robotic and laparotomy methods), and these varying surgical approaches might be responsible for their findings.

Furthermore, in view of the significant difference in total blood loss between the tranexamic acid group and the control observed in this study, it is not surprising that the mean postoperative haemoglobin concentration was higher in the tranexamic acid group than the control. Likewise, the mean difference in haemoglobin concentration was lower in the tranexamic acid group than the control group. This clearly showed that there was more blood loss in the control group compared with the study group, and since every other attribute was similar in the two groups, it can be assumed that tranexamic acid was responsible for the improved blood loss in the study group during the open myomectomy. This finding on mean postoperative haemoglobin concentration was similar to the report from Egypt.39 Conversely, reports from related studies from Turkey,36 Nairobi, Kenya,38 Egypt18 and Washington, USA14 did not find any significant difference regarding the mean postoperative haemoglobin concentration between the tranexamic acid group and the control. For the Washington study,14 the lack of difference in the total blood loss between the tranexamic acid and the control groups might explain the lack of a significant difference in the mean haemoglobin difference picture, but the explanation for the findings of the other studies that showed similar mean haemoglobin differences between the tranexamic group and the controls ^{18, 36, 38} is not clear. This difference could be attributed to the small sample size that was used in those studies.

It was also revealed from the study that the rates of blood transfusion during intraoperative and postoperative periods in the study and control groups, respectively, were significantly different. Showing that there were statistically significantly more blood transfusions, both intraoperatively and postoperatively, in the control group compared with the study groups.

The findings from the study on the rate of blood transfusion were similar to those from a study conducted in Aswan, Egypt.18 The authors found that the rate of blood transfusion was significantly higher in the control group (p=0.0001), and there was a significant difference between the study (intravenous tranexamic acid) group and the control group. Also, in a similar study in Ismaili, Egypt,39 the authors found that the rate of blood transfusion was significantly higher in the control group compared with the study group. They found that there were significantly more blood transfusions in women who did not use tranexamic acid during their study. This finding showed that tranexamic acid may reduce the rate of blood transfusions in myomectomies and its attendant complications.

A similar study in Nigeria37 found that although more transfusions per unit of blood (mean unit of blood) were given to the control group compared with the study group, their findings were not statistically different between the groups studied (p=0.256). Similarly, the study in Washington14 found that more blood transfusions were given to the control group compared with the study group. The studies in Turkey36 and Nairobi, Kenya38 also noted no significant difference between the study and control groups in terms of the rate of blood transfusion. The differences between our study and these other studies could be made clearer by more multicentre, large-population studies and meta-analyses. However, the usefulness of tranexamic acid in reducing blood loss during myomectomy in women who used tranexamic acid in addition to other blood-reducing strategies during myomectomy is convincing.

The study’s strength lies in its design as a double-blinded randomised placebo-controlled trial. The similarity in basic characteristics between the two groups indicates successful randomisation. While withdrawals can be common in clinical trials, the high retention rate in this study could be attributed to the diligent monitoring and support provided to participants throughout the study period. Although no withdrawals occurred, we accounted for potential attrition in our sample size calculation by including a 10% attrition rate, further adding to the strengths of the study. One of the limitations of our study was that the study focused on the amount of bleeding and haemoglobin levels during the surgery and the first 24 hours postoperatively but could not evaluate the patients’ long-term outcomes. We could not evaluate the cost-effectiveness of tranexamic acid as an adjunct to conventional tourniquet in minimising blood loss during open abdominal myomectomies. In addition, the more precise spectrophotometric haemoglobin analysis for blood loss assessment was not available; the gravimetric method used, though accurate, might have influenced the recorded blood loss quantity. However, this would not have impacted the observed effects of tranexamic acid. We also appreciate the fact that the type/location and the size of uterine fibroids may influence the extent of morbidities/complications, including the volume of intraoperative and postoperative blood loss. The primary analysis did not adjust for additional variables such as surgical difficulty, baseline characteristics or other potential confounders due to the homogeneity of the groups at baseline. However, the participants were randomised, hence the influence of type and size of uterine myoma as confounding variables were eliminated via the randomisation process. In the current study, we could not directly assess surgical difficulty as a separate variable, which may act as a confounder. Thus, we plan to explore these potential associations between surgical difficulty and outcomes in future randomised control trials.

Conclusion

Intraoperative blood loss for participants who received tranexamic acid in addition to the baseline tourniquet application was not significantly different from that of women who received only the tourniquet during open myomectomies. However, total blood loss and the need for blood transfusion were significantly lower in the tranexamic acid group compared with the control group, and so combining tranexamic acid with a tourniquet should be considered in gynaecological practice, especially in settings where large uterine fibroids are common. The results are expected to provide evidence that could inform policy formulation or modifications to global myomectomy guidelines for gynaecologists. Further high-quality randomised control trials are recommended to confirm the additional benefit of intravenous tranexamic acid in conjunction with routine tourniquets for blood loss reduction during open abdominal myomectomy.

Supplementary PDF

Supplementary spreadsheet

KEE and VIA are joint first authors.
Contributors: KEE and VIA, the principal investigators were involved in conceptualisation, manuscript writing, revision and data collection. JTE, CCD and GUE were involved in supervision, manuscript writing, revision and data analysis. DMA, CCO and CGO were involved in manuscript writing and revision. All authors proofread and approved the final copy for submission to the journal. VIA is the guarantor.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review: Not commissioned; externally peer reviewed.
Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. The study protocol is included as supplementary file 1.

Ethics statements

Patient consent for publication:

Ethics approval:

The ethical approval for the study was obtained from the Health Research Ethics Committee (HREC) of the two teaching hospitals and MOCSH (UNTH/CSA/329/VOL.5/010). The study was conducted according to ethical principles for human subjects according to the Helsinki Declaration. Participants gave informed consent to participate in the study before taking part. The authors adhered to CONSORT guidelines.

Acknowledgements

The authors wish to express our gratitude to the subjects who participated in the study, the research assistants and the management of the three hospitals used for the research for approving and providing the enabling environment for the study.

Madunatu CM, Okoro CC, Onyejiaka CC, et al. A 5-year retrospective review of the presentation pattern and management outcomes of uterine fibroids in a Nigerian tertiary Hospital. Int J Clin Obstet Gynaecol 2024; 8:15–9.
doi:10.33545/gynae.2024.v8.i1a.1410•Google Scholar
Li B, Wang F, Chen L, et al. Global epidemiological characteristics of uterine fibroids. Arch Med Sci 2023; 19:1802–10.
doi:10.5114/aoms/171786•Google Scholar
Awoyesuku PA, MacPepple DA, Altraide BO, et al. Review of gynaecological diagnoses and surgeries performed at a tertiary health facility in Niger-Delta of Nigeria from 2012-2017: Implications for healthcare planning and budgeting. JAMMR 2020; 3:1–10.
doi:10.9734/jammr/2020/v32i230361•Google Scholar
Gupta AK, Gupta I, Suri AK, et al. Histopathological spectrum of hysterectomy specimens. JAMMR 2020; 32:96–104.
doi:10.9734/jammr/2020/v32i630440•Google Scholar
Irechukwu JC, Eleje GU, Iwe BC, et al. A randomized controlled trial of rectal versus intramuscular diclofenac for post-operative analgesia after open myomectomy. Eur J Obstet Gynecol Reprod Biol 2024; 292:244–50.
doi:10.1016/j.ejogrb.2023.11.029•Google Scholar
Okoro CC, Ikpeze OC, Eleje GU, et al. Association between serum vitamin D status and uterine leiomyomas: a case-control study. Obstet Gynecol Sci 2024; 67:101–11.
doi:10.5468/ogs.23143•Google Scholar
Nnagbo JE, Dim CC, Eze MI, et al. Effects of misoprostol in reducing blood loss during abdominal myomectomy in Nigeria. Niger J Clin Pract 2023; 26:454–62.
doi:10.4103/njcp.njcp_526_22•Google Scholar
Okogbo FO, Ezechi OC, Loto OM, et al. Uterine leiomyomata in south western Nigeria: A clinical study of presentation and management outcome. Afri Health Center 2011; 2:271–8.
Google Scholar
Sefah N, Ndebele S, Prince L, et al. Uterine fibroids - Causes, impact, treatment, and lens to the African perspective. Front Pharmacol 2022; 13.
doi:10.3389/fphar.2022.1045783•Google Scholar
Ikechebelu JI, Okpala BC, Eleje GU, et al. Delayed presentation of giant uterine fibroids in a Nigerian private specialist health facility. SAGE Open Med Case Rep 2021; 9.
doi:10.1177/2050313X211063137•Google Scholar
Cheng L-C, Li H-Y, Gong Q-Q, et al. Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 Global Burden of Disease Study. Front Med (Lausanne) 2022; 9.
doi:10.3389/fmed.2022.1003605•Google Scholar
Omokanye LO, Salaudeen CA, Saidu R, et al. Surgical management of uterine fibroid at the Uni. Of Ilorin teaching Hospital: A 5-year review. Global Research J of Med 2012; 2:018–22.
Google Scholar
Pundir J, Krishnan N, Siozos A, et al. Peri-operative morbidity associated with abdominal myomectomy for very large fibroid uteri. Eur J obstet Gynaecol Reprod Biol 2013; 167:219–24.
doi:10.1016/j.ejogrb.2012.12.010•Google Scholar
Raga F, Sanz-Cortes M, Bonilla F, et al. Reducing blood loss at myomectomy with use of a gelatin-thrombin matrix hemostatic sealant. Fertil Steril 2009; 92:356–60.
doi:10.1016/j.fertnstert.2008.04.038•Google Scholar
Yuk JS, Kim M. Incidence rates of myomectomy-related mortality and venous thromboembolism in South Korea: A population-based study. Front Med (Lausanne) 2022; 9.
doi:10.3389/fmed.2022.849660•Google Scholar
Saha MM, Biswas SC, Alam H, et al. Assessment of blood loss in abdominal myomectomy by intramyometrial vasopressin administration versus conventional tourniquet application. J Clin Diagn Res 2016; 10:QC10–3.
doi:10.7860/JCDR/2016/17484.7789•Google Scholar
Ikechebelu JI, Ezeama CO, Obiechina NJA, et al. The use of tourniquet to reduce blood loss at myomectomy. Niger J Cline Pract 2010; 13:154–8.
Google Scholar
Shady NW, Sallam HF, Fahmy H, et al. Reducing blood loss during open myomectomy with intravenous versus topical tranexamic acid: A double-blinded randomized placebo-controlled trial. Middle East Fertil Soc J 2018; 23:225–31.
doi:10.1016/j.mefs.2017.12.010•Google Scholar
Cap AP, Baer DG, Orman JA, et al. Tranexamic acid for trauma patients: a critical review of the literature. J Trauma 2011; 71:S9–14.
doi:10.1097/TA.0b013e31822114af•Google Scholar
Henry DA, Carless PA, Moxey AJ, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2011; 16.
doi:10.1002/14651858.CD001886.pub3•Google Scholar
Wang C, Xu G, Han Z, et al. Topical application of tranexamic acid in primary total hip arthroplasty: a systemic review and meta-analysis. Int J Surg 2015; 15:134–9.
doi:10.1016/j.ijsu.2014.12.023•Google Scholar
Massicotte L, Denault AY, Beaulieu D, et al. Aprotinin versus tranexamic acid during liver transplantation: Impact on blood product requirements and survival. Transplantation 2011; 91:1273–8.
doi:10.1097/TP.0b013e31821ab9f8•Google Scholar
Ortuanya KE, Eleje GU, Ezugwu FO, et al. Prophylactic tranexamic acid for reducing intraoperative blood loss during cesarean section in women at high risk of postpartum hemorrhage: A double-blind placebo randomized controlled trial. Womens Health (Lond Engl) 2024; 20:17455057231225311.
doi:10.1177/17455057231225311•Google Scholar
Zakhari A, Sanders AP, Solnik MJ, et al. Tranexamic acid in gynecologic surgery. Curr Med Res Opin 2020; 36:513–20.
doi:10.1080/03007995.2019.1708533•Google Scholar
Kathopoulis N, Prodromidou A, Zacharakis D, et al. The effect of intravenous tranexamic acid on myomectomy: A systematic review and meta-analysis of randomized controlled trials. J Pers Med 2022; 12.
doi:10.3390/jpm12091492•Google Scholar
Baradwan S, Hafidh B, Latifah HM, et al. Prophylactic tranexamic acid during myomectomy: A systematic review and meta-analysis of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol 2022; 276:82–91.
doi:10.1016/j.ejogrb.2022.07.004•Google Scholar
Olaleye AA, Adebayo JA, Eze JN, et al. Efficacy of tranexamic acid in reducing myomectomy-associated blood loss among patients with uterine myomas at federal teaching hospital Abakaliki: A randomized control trial. Int J Reprod Med 2024; 2024.
doi:10.1155/2024/2794052•Google Scholar
Fusca L, Perelman I, Fergusson D, et al. The effectiveness of tranexamic acid at reducing blood loss and transfusion requirement for women undergoing myomectomy: A systematic review and meta-analysis. J Obstet Gynaecol Can 2019; 41:1185–92.
doi:10.1016/j.jogc.2018.04.007•Google Scholar
Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy for fibroids. Cochrane Database Syst Rev 2011; 8.
doi:10.1002/14651858.CD005355.pub4•Google Scholar
Afolabi MA, Ezeoke GG, Saidu R, et al. Comparing perioperative vaginal misoprostol with intraoperative pericervical hemostatic tourniquet in reducing blood loss during abdominal myomectomy: A randomized controlled trial. J Turkish German Gynecol Assoc 2019; 20:23–30.
doi:10.4274/jtgga.galenos.2018.2018.0049•Google Scholar
Ndububa VI. Uterine fibroids: Experience with 100 myomectomies in Orlu, South East Nigeria. Port Harcourt Med J 2016; 10:124.
doi:10.4103/0795-3038.197753•Google Scholar
Frascà C, Tuzzato G, Arena A, et al. The role of pelvic ultrasound in preoperative evaluation for laparoscopic myomectomy. J Minim Invasive Gynecol 2018; 25:679–83.
doi:10.1016/j.jmig.2017.08.661•Google Scholar
Allen JC, van Belle B. Sample size calculations for two independent groups: a useful rule of the thumb, Statistical rule of thumb. 1ed. New York. NY, Willey interscience 2002;
Google Scholar
Camry digital kitchen weighing scale model EK 3250 ISO 9001:2015.
Google Scholar
Kane Z, Picetti R, Wilby A, et al. Physiologically based modelling of tranexamic acid pharmacokinetics following intravenous, intramuscular, sub-cutaneous and oral administration in healthy volunteers. Eur J Pharm Sci 2021; 164.
doi:10.1016/j.ejps.2021.105893•Google Scholar
Caglar GS, Tasci Y, Kayikcioglu F, et al. Intravenous tranexamic acid use in myomectomy: a prospective randomized double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol 2008; 137:227–31.
doi:10.1016/j.ejogrb.2007.04.003•Google Scholar
Abdul IF, Amadu MB, Adesina KT, et al. Adjunctive use of tranexamic acid to tourniquet in reducing haemorrhage during abdominal myomectomy - A randomized controlled trial. Eur J Obstet Gynecol Reprod Biol 2019; 242:150–8.
doi:10.1016/j.ejogrb.2019.09.010•Google Scholar
Ngichabe S, Obura T, Stones W, et al. Intravenous tranexamic acid as an adjunct haemostat to ornipressin during open myomectomy. A randomized double blind placebo controlled trial. Ann Surg Innov Res 2015; 9.
doi:10.1186/s13022-015-0017-y•Google Scholar
Shaabam M, Ahmed M, Farham RS, et al. Efficacy of tranexamic acid on myomectomy associated blood loss in patient with multiple myoma (RCT). Reprod Sci 2016; 23:908–12.
Google Scholar

Received: 13 August 2024
Accepted: 23 March 2025
First published: 28 April 2025

Pre-publication versions•Review history

Overview

Abstract
Introduction
Methods
Results
Discussion
Conclusion
References
Supplementary files
Footnotes
Publication history
Responses

Article metrics

Altmetric data not available for this article.

Dimensions